Fluid mechanics, cell distribution, and environment in CellCube bioreacors
Fluid mechanics, cell distribution, and environment in CellCube bioreacors
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DOI：
10.1021/bp0256521
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发表时间：
2003-01-01
影响因子：
2.9
通讯作者：
Zhou, WC
中科院分区：
文献类型：
--
作者：
Aunins, JG;Bader, B;Zhou, WC
为了生产甲型肝炎灭活疫苗VAQTA，培养MRC-5细胞和减毒甲型肝炎病毒(HAV)是在Cellcube反应器中进行的，该反应器是一种层流固定床生物反应器，具有独特的菱形、发散-会聚流动几何结构。这些一次性生物反应器已被用于生产中等规模的细胞和基因治疗载体(2，)。对细胞立方体的早期测试表明，流体机械环境在细胞生长阶段产生的不均匀细胞分布模式中起着重要作用。具体地说，反应器的几何形状和制造工艺，与某些接种实践和循环流速相结合，可以创造出无法简单解释的细胞生长行为。通过实验和计算流体力学模拟，我们可以解释几乎所有观察到的细胞生长行为，这似乎是由于流动分布、重力下的颗粒沉积、流体剪切以及可能的营养微环境的复杂混合物造成的。
Cultivation of MRC-5 cells and attenuated hepatitis A virus (HAV) for the production of VAQTA, an inactivated HAV vaccine (1), is performed in the CellCube reactor, a laminar flow fixed-bed bioreactor with an unusual diamond-shaped, diverging-converging flow geometry. These disposable bioreactors have found some popularity for the production of cells and gene therapy vectors at intermediate scales of operation (2,). Early testing of the CellCube revealed that the fluid mechanical environment played a significant role in nonuniform cell distribution patterns generated during the cell growth phase. Specifically, the reactor geometry and manufacturing artifacts, in combination with certain inoculum practices and circulation flow rates, can create cell growth behavior that is not simply explained. Via experimentation and computational fluid dynamics simulations we can account for practically all of the observed cell growth behavior, which appears to he due to a complex mixture of flow distribution, particle deposition under gravity, fluid shear, and possibly nutritional microenvironment.